The study was designed to evaluate the pharmacokinetics of physostigmine in patients with Alzheimer's Disease. We also attempted to correlate steady- state plasma concentrations with both cognitive improvement and adverse effects. Patients were given a continuous IV infusion of physostigmine over a period of six hours. Patients began with an infusion rate of 0.1 mg/hr and the rate was increased no more than 50 percent per day. Whole blood samples were collected at 0 time, every hour until the infusion was stopped and then every 10 minutes for 60 minutes, thereafter. Samples were collected in cold (0 degrees C) heparinized tubes which contained neostigmine bromide (50 ml/nl, 5 mg/ml solution). Plasma was separated by centrifugation and stored until analysis. Samples were quantitated using an HPLC fluorescence method developed in our laboratory.